研究者詳細 - 杉本　誠一郎

Sacrificing the pulmonary arterial branch to the spared lobe is a risk factor of bronchopleural fistula in sleeve lobectomy after chemoradiotherapy 査読国際誌

Shinichi Toyooka, Junichi Soh, Kazuhiko Shien, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Hiroshi Date, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 43 ( 3 ) 568 - 572 2013年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS INC

A sleeve lobectomy is a widely accepted procedure for enabling the pulmonary parenchyma to be spared. Induction chemoradiotherapy (CRT) followed by surgery is one treatment option for locally advanced non-small cell lung cancer (NSCLC), but CRT is considered to have a negative effect on subsequent surgery, especially for anastomotic healing. In this study, we describe our experience performing sleeve lobectomies and the associated anastomotic complications after induction CRT.
The medical records of NSCLC patients who underwent surgery after receiving CRT were reviewed. The relationships between anastomotic complications and clinicopathological factors were examined.
Between December 1998 and October 2011, a total of 104 patients received CRT followed by surgery. Among them, 14 NSCLC patients underwent a bronchial sleeve resection: nine patients underwent a right upper lobe resection, two patients underwent a left lingular division and lower lobe resection and one patient each underwent a right lower lobe, a right upper and middle lobe and a right middle and lower lobe resection. A bronchopleural fistula at the anastomosis occurred in two patients. A pulmonary arterial (PA) branch to the spared lobe had been sacrificed in both of these patients because of tumour involvement. In contrast, the PA branches to the spared lobes were preserved in 11 of the 12 patients who did not exhibit anastomotic complications (P = 0.033).
Our experience strongly suggests that the sacrifice of the PA branch to the spared lobe is a possible risk factor for anastomotic complications for a sleeve lobectomy after induction CRT.

DOI： 10.1093/ejcts/ezs323

「COPDの集学的治療」嚢胞性肺疾患に対する肺移植治療

岡田真典, 大藤剛宏, 伊賀徳周, 原田昌明, 西川仁士, 中谷文, 三好健太郎, 大谷真二, 杉本誠一郎, 宗淳一, 山根正修, 豊岡伸一, 三好新一郎

日本気胸・嚢胞性肺疾患学会雑誌 12 ( 2 ) 121 - 124 2012年11月

記述言語：日本語出版者・発行元：日本気胸・嚢胞性肺疾患学会

肺移植手術を施行した87例を嚢胞性肺疾患28例(男9例、女19例、平均32.4歳;A群)と非嚢胞性肺疾患59例(男18例、女42例、平均32.7歳;B群)に分け、成績を比較した。年齢、性別、術式(生体/脳死肺移植)は両群間で有意差がなかった。術後人工呼吸器管理日数およびICU滞在日数はA群が良好であったが、術後入院期間は両群間で有意差はなかった。術後ADL評価としてHugh-Johns分類の推移と6分間歩行値を比較したが、両群間で有意差はなく、共に術前より大幅に改善していた。呼吸機能については、術前にA群でFEV1.0、FEV1.0%、PaCO2が有意に悪化していたが、術後は両群間で有意差がなくなり、%VC、P/F ratioは術前後とも有意差はなかった。慢性拒絶反応(BOS)の無発症期間はA群中央値55ヵ月、B群43ヵ月、5年生存率はそれぞれ87.7%、74.6%で、有意差はなかった。A群では3例にBOSを認め、1例に再肺移植を施行した。

Intrathoracic irrigation with arbekacin for methicillin-resistant Staphylococcus aureus empyema following lung resection 査読国際誌

Tsuyoshi Ueno, Shinichi Toyooka, Junichi Soh, Kentaroh Miyoshi, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Shinichiro Miyoshi

INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY 15 ( 3 ) 437 - 441 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

OBJECTIVES: Empyema is a well-known complication following lung resection. In particular, empyema caused by methicillin-resistant Staphylococcus aureus (MRSA) is difficult to treat. Here, we present our experience of MRSA empyema treated with local irrigation using arbekacin.
METHODS: Six patients consisted of 4 males and 2 females with an average age of 65.7 years. They developed MRSA empyema following lung resection and were treated at our institution between 2007 and 2011. Cases comprised four primary and one metastatic lung cancer, and 1 patient was a living lung transplantation donor. The surgical procedure consisted of four lobectomies, one segmentectomy and one wedge resection. After diagnosis of MRSA empyema, anti-MRSA drugs were administered intravenously in all cases. In addition, arbekacin irrigation at a dose of 100 mg dissolved in saline was performed after irrigation with saline only.
RESULTS: The average number of postoperative days for the diagnosis of MRSA empyema was 13 (range 4-19). The period of irrigation ranged from 6 to 46 days. Arbekacin irrigation did not induce nephrotoxicity or other complications, and no bacteria resistant to arbekacin was detected in the thoracic cavity. We re-operated on 1 case because he had pulmonary fistula and severe wound infection. At the time of removing the thoracic catheter, MRSA in the pleural effusion disappeared completely in 3 patients. The period until MRSA concentration in the pleural effusion became negative after starting arbekacin irrigation ranged from 4 to 9 days. In the remaining cases, in which MRSA did not disappear, the catheter was removed because of no inflammatory reaction after stopping irrigation and clamping the catheters. All patients were discharged from our institution without thoracic catheterization and no patients had relapsed during the follow-up period ranging from 6 to 44 months.
CONCLUSIONS: Irrigation of the thoracic cavity with arbekacin proved to be an effective, safe and readily available method for treating MRSA empyema following lung resection.

DOI： 10.1093/icvts/ivs285

Outcome of living-donor lobar lung transplantation using a single donor 査読国際誌

Hiroshi Date, Takeshi Shiraishi, Seiichiro Sugimoto, Tsuyoshi Shoji, Fengshi Chen, Masafumi Hiratsuka, Akihiro Aoyama, Masaaki Sato, Masaomi Yamane, Akinori Iwasaki, Shinichiro Miyoshi, Toru Bando, Takahiro Oto

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 144 ( 3 ) 710 - 715 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MOSBY-ELSEVIER

Objective: Living-donor lobar lung transplantation usually requires 2 healthy donors who donate either a right or a left lower lobe; however, finding 2 healthy donors is difficult. Several case reports have been published on successful living-donor lobar lung transplantation using a single donor; however, little is known about its outcome.
Methods: We retrospectively investigated 14 critically ill patients who had undergone single living-donor lobar lung transplantation at 3 lung transplant centers in Japan. There were 10 female and 4 male patients, including 10 children and 4 adults. Size matching was assessed by estimated graft forced vital capacity and 3-dimensional computed tomography volumetry. The diagnoses included complications of allogeneic hematopoietic stem cell transplantation (n = 6), pulmonary hypertension (n = 4), and others (n = 4).
Results: At a mean follow-up of 45 months (range, 2-128), the 3- and 5-year survival rate was 70% and 56%, respectively. There were 4 early deaths, for a hospital mortality of 29%, with 1 additional death at 40 months. The main cause of early death was primary graft dysfunction, most likely related to size mismatching. The survival among these 14 patients was significantly worse than the survival in a group of 78 patients undergoing bilateral living-donor lobar lung transplantation during the same period (P = .044).
Conclusions: Single living-donor lobar lung transplantation provides acceptable results for sick patients who would die soon otherwise. However, bilateral living-donor lobar lung transplantation appears to be a better option if 2 living donors are found. (J Thorac Cardiovasc Surg 2012; 144: 710-5)

DOI： 10.1016/j.jtcvs.2012.05.054

[Primary mediastinal lymphoma; a clinicopathologic case series]. 査読

Seiichiro Sugimoto, Junichi Soh, Yuho Maki, Takeshi Kurosaki, Masaomi Yamane, Shinichi Toyooka, Takahiro Oto, Shinichiro Miyoshi

Kyobu geka. The Japanese journal of thoracic surgery 65 ( 7 ) 527 - 31 2012年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Treatment for primary mediastinal lymphoma generally involves chemotherapy and radiotherapy, and treatment regimens depend on histologic subtypes of lymphoma. The histologic subtype of lymphoma is mostly determined by computed tomography (CT)-guided core-needle biopsy or surgical procedures, including thoracotomy, thoracoscopy and mediastinoscopy. We describe the clinicopathologic features and diagnostic procedures of 8 cases of primary mediastinal lymphoma. The male-to-female ratio was 1:1, and median age at diagnosis was 27 years. The median size of the primary mediastinal tumor on CT was 8.5 cm. Five patients were diagnosed by CT-guided core-needle biopsy, 1 by open biopsy and 2 by surgery. Three patients were diagnosed with nodular sclerosis Hodgkin lymphoma, 3 with mediastinal diffuse large B-cell lymphoma, 1 with precursor T-lymphoblastic leukemia/lymphoma and 1 with thymic extranodal marginal zone B-cell lymphoma. According to their histological subtypes, 5 patients were treated with chemoradiotherapy, 2 patients with chemotherapy and 1 patient of thymic extranodal marginal zone B-cell lymphoma with surgery alone. All patients survived in the median follow-up of 34.5 months. Appropriate biopsy procedure should be performed in patients with suspected mediastinal lymphoma.

A Case of Delayed Massive Hemothorax Caused by the Rupture of a Pulmonary Artery Pseudoaneurysm after Radiofrequency Ablation of Lung Tumors 査読国際誌

Junichi Soh, Shinichi Toyooka, Hideo Gobara, Takao Hiraki, Seiichiro Sugimoto, Masaomi Yamane, Takahiro Oto, Susumu Kanazawa, Shinichiro Miyoshi

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 42 ( 7 ) 646 - 649 2012年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

Radiofrequency ablation has been applied as a minimally invasive therapy for the local control of lung tumors, including primary and metastatic neoplasms. Hemorrhagic complications after radiofrequency ablation can usually be treated conservatively, but such complications can be massive and fatal in some cases. In this paper, we report the rare case of delayed massive hemothrax caused by the rupture of a pulmonary artery pseudoaneurysm after lung radiofrequency ablation that was treated using transcatheter coil embolization followed by a left lower lobectomy. A 75-year-old woman underwent radiofrequency ablation for the treatment of a metastatic lung tumor in the left lower lobe arising from a colorectal carcinoma located close to a branch of the pulmonary artery. Thirty-six hours later, hemothorax and hemorrhagic shock occurred as a result of a ruptured pulmonary artery pseudoaneurysm and radiofrequency ablation-induced damage to the interlobular pleura. After transcatheter coil embolization of the pulmonary artery pseudoaneurysm, she recovered from a state of shock and a left lower lobectomy was performed. Histological findings revealed the presence of residual tumor cells in the ablated lung tumor. The postoperative course was uneventful, and no evidence of recurrence of the primary disease was seen at 1 year after the surgery. Although hemothorax secondary to the rupture of a pulmonary artery pseudoaneurysm after lung radiofrequency ablation is a rare complication, it should be recognized as a serious potential complication of lung radiofrequency ablation for a tumor located close to the pulmonary artery branch.

DOI： 10.1093/jjco/hys068

「高齢化社会を迎えての臓器移植の展望:高齢ドナー移植の現状と問題」肺移植における高齢ドナー

大藤剛宏, 三好健太郎, 杉本誠一郎, 山根正修, 三好新一郎

移植 47 ( 2/3 ) 161 - 165 2012年6月

Five-year update on the mouse model of orthotopic lung transplantation: Scientific uses, tricks of the trade, and tips for success 査読国際誌

Xue Lin, Wenjun Li, Jiaming Lai, Mikio Okazaki, Seiichiro Sugimoto, Sumiharu Yamamoto, Xingan Wang, Andrew E. Gelman, Daniel Kreisel, Alexander Sasha Krupnick

JOURNAL OF THORACIC DISEASE 4 ( 3 ) 247 - 258 2012年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PIONEER BIOSCIENCE PUBL CO

It has been 5 years since our team reported the first successful model of orthotopic single lung transplantation in the mouse (1). There has been great demand for this technique due to the obvious experimental advantages the mouse offers over other large and small animal models of lung transplantation. These include the availability of mouse-specific reagents as well as knockout and transgenic technology. Our laboratory has utilized this mouse model to study both immunological and non-immunological mechanisms of lung transplant physiology while others have focused on models of chronic rejection (1-19). It is surprising that despite our initial publication in 2007 only few other laboratories have published data using this model (20-25). This is likely due to the technical complexity of the surgical technique and perioperative complications, which can limit recipient survival (9,26). As two of the authors (XL and WL) have a combined experience of over 2500 left and right single lung transplants, this review will summarize their experience and delineate tips and tricks necessary for successful transplantation. We will also describe technical advances made since the original description of the model (1,5,6).

DOI： 10.3978/j.issn.2072-1439.2012.06.02

Egr1: a novel target for ameliorating acute allograft rejection in an experimental lung transplant model 査読国際誌

Naohisa Waki, Masaomi Yamane, Sumiharu Yamamoto, Mikio Okazaki, Seiichiro Sugimoto, Akihiro Matsukawa, Takahiro Oto, Shinichiro Miyoshi

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY 41 ( 3 ) 669 - 675 2012年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS INC

Acute allograft rejection is one of the significant complications occurring in lung transplant recipients. Early growth response-1 (Egr-1), zinc-finger-type transcription factor, is known as a master switch regulator of diverse chemical mediators. We used an orthotopic mouse model of left lung transplant to elucidate the function of Egr-1 in acute pulmonary rejection.
Left lung grafts retrieved from C57BL/6 wild mice or C57BL/6 Egr-1-null mice were orthotopically transplanted into BALB/c mice; the lungs were harvested at day 1, 3, 5 or 7 after lung transplantation. The grade of acute rejection was histopathologically evaluated. The intragraft gene expression levels of Egr-1 and downstream target mediators were quantitatively measured by real-time polymerase chain reaction. Immunohistochemical analysis was used to determine the location and distribution of the Egr-1 protein in the pulmonary graft.
Severe acute rejection was observed in allografts from wild-type mice at 5 days after transplantation. Only minimal rejection was seen in the lung graft from Egr-1-null donor mice at 5 days after transplantation. Strong upregulation of Egr-1 mRNA transcripts was observed at day 1, which then decreased during the next 5 days. The mRNA of Egr-1 target mediators [interleukin-1-beta (IL-1 beta), monocyte chemotactic protein-1 (MCP-1) and plasminogen activator inhibitor-1] reached maximal levels at day 5. Egr-1-null allografts exhibited significantly lower expressions of IL-1 beta and MCP-1 mRNA (P < 0.05).
Our study showed that deletion of Egr-1 in lung allografts ameliorates severe acute rejection with the reduction of expression levels of chemical mediators, implying a new possible strategy for treating acute pulmonary allograft rejection.

DOI： 10.1093/ejcts/ezr030

「切除困難例」への化学療法後の手術―根治切除はどこまで可能か非小細胞肺癌に対する根治的放射線化学療法後の手術

豊岡伸一, 宗淳一, 枝園和彦, 牧佑歩, 三好健太郎, 上野剛, 杉本誠一郎, 山根正修, 大藤剛宏, 三好新一郎

臨床外科 67 ( 1 ) 12 - 16 2012年1月

記述言語：日本語出版者・発行元：(株)医学書院

＜ポイント＞◆局所進行非小細胞肺癌に対しては根治的放射線化学療法を行うことが多いが,その後,外科手術になることがある.◆根治的放射線化学療法の再発症例に対するサルベージ手術,あるいは高線量による導入放射線化学療法の有用性は確立していない.◆高線量の放射線照射後の手術はリスクが高くなることが考えられるが,手術が原病,あるいは治療による合併症を改善する症例があり,必要に応じて手術を考慮すべきである.(著者抄録)

DOI： 10.11477/mf.1407103898

Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance 査読国際誌

Daniel Kreisel, Seiichiro Sugimoto, Jihong Zhu, Ruben Nava, Wenjun Li, Mikio Okazaki, Sumiharu Yamamoto, Mohsen Ibrahim, Howard J. Huang, Kelsey A. Toth, Jon H. Ritter, Alexander S. Krupnick, Mark J. Miller, Andrew E. Gelman

BLOOD 118 ( 23 ) 6172 - 6182 2011年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC HEMATOLOGY

The mechanisms by which innate immune signals regulate alloimmune responses remain poorly understood. In the present study, we show by intravital 2-photon microscopy direct interactions between graft-infiltrating neutrophils and donor CD11c(+) dendritic cells (DCs) within orthotopic lung allografts immediately after reperfusion. Neutrophils isolated from the airways of lung transplantation recipients stimulate donor DCs in a contact-dependent fashion to augment their production of IL-12 and expand alloantigen-specific IFN-gamma(+) T cells. DC IL-12 expression is largely regulated by degranulation and induced by TNF-alpha associated with the neutrophil plasma membrane. Extended cold ischemic graft storage enhances G-CSF-mediated granulopoiesis and neutrophil graft infiltration, resulting in exacerbation of ischemia-reperfusion injury after lung transplantation. Ischemia reperfusion injury prevents immunosuppression-mediated acceptance of mouse lung allografts unless G-CSF-mediated granulopoiesis is inhibited. Our findings identify granulopoiesis-mediated augmentation of alloimmunity as a novel link between innate and adaptive immune responses after organ transplantation. (Blood. 2011;118(23):6172-6182)

DOI： 10.1182/blood-2011-04-347823

縦隔リンパ節転移を伴った肺癌に対する外科的治療をめぐって 3.術前化学療法後外科的治療 1)術前放射線化学療法における外科治療の役割

豊岡伸一, 宗淳一, 杉本誠一郎, 山根正修, 大藤剛宏, 三好新一郎

日本胸部臨床 70 ( 9 ) 919 - 924 2011年9月

記述言語：日本語出版者・発行元：克誠堂出版(株)

縦隔リンパ節転移を伴う非小細胞肺癌に対する手術の意義が問われている。導入放射線化学療法後手術群と根治的放射線化学療法群の生存率を比較した第III相試験(Intergroup trail 1346)の結果が発表されたが、全症例に対する解析では手術の有用性は確認できなかった。しかしながらこの試験では肺全摘症例の術後早期の死亡例が多く、肺葉切除に限った場合では手術群が放射線抗癌薬のみの群より良好な成績であり、手術の有用性が示唆されている。当院ではN2肺癌に対し1995年より術前導入療法後手術療法を行ってきた。特に放射線化学療法後手術を行う症例の成績は良好であり、有用な治療法として位置付けている。(著者抄録)

法改正後の移植の現状と問題点:心肺領域マージナル肺ドナーとメディカルコンサルタント

大藤剛宏, 三好健太郎, 杉本誠一郎, 山根正修, 三好新一郎

移植 46 ( 4/5 ) 281 - 283 2011年9月

治療抵抗性特発性間質性肺炎に対する生体肺移植

三好健太郎, 大藤剛宏, 大谷真二, 杉本誠一郎, 宗淳一, 山根正修, 豊岡伸一, 三好新一郎

臨床呼吸生理 43 47 - 49 2011年6月

記述言語：日本語出版者・発行元：臨床呼吸生理研究会

生体肺移植を行った56例を難治性特発性間質性肺炎14例(男4例、女10例、平均41.8歳;IIP群)と他疾患42例(男9例、女33例、平均27.9歳;non-IIP群)に分け、急性期および慢性期評価を比較した。年齢、術前ステロイド使用頻度はIIP群で高い傾向であった。術後ICU滞在平均日数はIIP群20.4日、non-IIP群34.4日、術後3ヵ月の6分間歩行はそれぞれ371.7m、353.7mで、いずれも有意差はなかった。慢性拒絶反応無発症期間はIIP群中央値52ヵ月、non-IIP群56ヵ月、生存期間はそれぞれ67ヵ月、73ヵ月と有意差はなく、両群とも良好に経過している。肺移植後の呼吸機能は、1秒率は両群で同様の改善傾向を認めたが、%努力性肺活量はIIP群がnon-IIP群と比較して術後早期からの回復が認められた。

A novel technique for identification of the lung intersegmental plane using dye injection into the segmental pulmonary artery 査読国際誌

Seiichiro Sugimoto, Takahiro Oto, Kentaroh Miyoshi, Shinichiro Miyoshi

JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 141 ( 5 ) 1325 - 1327 2011年5月

Maintenance of IKKβ activity is necessary to protect lung grafts from acute injury. 査読国際誌

Huang HJ, Sugimoto S, Lai J, Okazaki M, Yamamoto S, Krupnick AS, Kreisel D, Gelman AE

Transplantation 91 ( 6 ) 624 - 631 2011年3月

Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis 査読国際誌

Daniel Kreisel, Seiichiro Sugimoto, Jeremy Tietjens, Jihong Zhu, Sumiharu Yamamoto, Alexander S. Krupnick, Ruaidhri J. Carmody, Andrew E. Gelman

JOURNAL OF CLINICAL INVESTIGATION 121 ( 1 ) 265 - 276 2011年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC CLINICAL INVESTIGATION INC

Granulocytes are pivotal regulators of tissue injury However, the transcriptional mechanisms that regulate granulopoiesis under inflammatory conditions are poorly understood Here we show that the transcriptional coregulator B cell leukemia/lymphoma 3 (Bcl3) limits granulopoiesis under emergency e, inflammatory) conditions, but not homeostatic conditions Treatment of mouse myeloid progenitors with G-CSF serum concentrations of which rise under inflammatory conditions rapidly increased Bcl3 transcript accumulation in a STAT3-dependent manner Bcl3-deficient myeloid progenitors demonstrated an enhanced capacity to proliferate and differentiate into granulocytes following G-CSF stimulation, whereas the accumulation of Bcl3 protein attenuated granulopoiesis in an NF-kappa B p50-dependent manner In a clinically relevant model of transplant-mediated lung ischemia reperfusion injury, expression of Bcl3 in recipients inhibited emergency granulopoiesis and limited acute graft damage These data demonstrate a critical role for Bcl3 in regulating emergency granulopoiesis and suggest that targeting the differentiation of myeloid progenitors may be a therapeutic strategy for preventing inflammatory lung injury

DOI： 10.1172/JCI42596